The research supported by this program-project grant provides an integrated approach to the elucidation of the nature of the carcinogenic process. The studies in Drs. J.A. and E.C. Miller's group are primarily concerned with the early steps in the carcinogenic process -- i.e., the nature of the ultimate carcinogenic derivatives, the identities of macromolecular adducts formed from them in vivo, and the consequences of the interactions of the carcinogens with DNA or other macromolecules. The research in Dr. Boutwell's laboratory seeks to elucidate the molecular nature of promotion, especially in mouse skin. Dr. H.C. Pitot and Dr. V.R. Potter are both analyzing aspects of the initiation and promotion of hepatic carcinogenesis. Both of these research groups are also analyzing aspects of the metabolic capacity of liver in cell culture as compared with that in the whole animal in relation to the controls introduced by various hormonal situations and other modifying agents. Dr. Poland's work has centered on the examination of the toxicity of 2, 3, 7, 8-tetracholor-p-dioxin, a compound of considerable interest in view of its high toxicity and the development of tumors in rats given very low doses.